Phosphorus oxychloride → 4-Methylthiazole-2-carboxylic acid (2-acetyl-5-methoxyphenyl)amide

HRID 1815714Notes

Reaction equation

[NH2:1][C:2]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:3]=1[C:4]([C:6]1C=CC=CC=1)=[O:5].[CH:18]([C:21]1[N:22]=[C:23]([C:26](O)=[O:27])[S:24][CH:25]=1)(C)C.O=P(Cl)(Cl)Cl>N1C=CC=CC=1>[C:4]([C:3]1[CH:12]=[CH:13][C:14]([O:16][CH3:17])=[CH:15][C:2]=1[NH:1][C:26]([C:23]1[S:24][CH:25]=[C:21]([CH3:18])[N:22]=1)=[O:27])(=[O:5])[CH3:6]

Participants

Conditions

Temperature: -30 °C

Procedure

To a suspension of 2.59 g (15.7 mmol) of 2-amino-4-methoxybenzophenone (product of step D) and 2.68 g (15.7 mmol) of 4-isopropylthiazole-2-carboxylic acid (product of step 77c) in 75 mL of pyridine cooled to −30° C., was added 1.93 mL (23.5 mmol) of POCl3 slowly dropwise over 5 min. The mixture was stirred 3 h, warmed to room temperature and was stirred overnite. The reaction mixture was poured into ice water, and extracted several times with EtOAc. The combined EtOAc extracts were dried (MgSO4), concentrated and chromatographed over SiO2 (eluted with 0% to 15% MeOH/EtOAc) to afford 2.57 g (51%) of 4-Methylthiazole-2-carboxylic acid (2-acetyl-5-methoxyphenyl)amide as a yellow solid: 1H NMR (CDCl3) δ ppm 1.41 (d, J=6.7 Hz, 6H), 2.64 (s, 3H), 3.24 (m, 1H), 3.91 (s, 3H), 6.67 (dd, J=9, 2.5 Hz, 1H), 7.18 (s, 1H), 7.86 (d, J=9 Hz, 1H), 8.56 (d, J=2.5 Hz, 1H), 13.48 (s, 1H).

Workup

temperaturewarmed to room temperature
stirringwas stirred overnite
extractionextracted several times with EtOAc
dry with materialThe combined EtOAc extracts were dried (MgSO4)
concentrationconcentrated
customchromatographed over SiO2 (eluted with 0% to 15% MeOH/EtOAc)

Sources & evidence

ORD record: ord-f391162180dc4c39accd00e9ca772d5c
Source dataset: uspto-grants-2005_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06878722B2

Reaction notes

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